The following synthesis is not meant to be carried out by a
novice chemist, although it is not terribly difficult. For descriptions of how
to carry out the procedures, you should buy a standard lab procedures reference
manual (or preferably you should take college organic chemistry).
To a well stirred, cooled mixture of 34g of 30% H202 (hydrogen peroxide) in 150g 80% HCO2H (formic acid) there was added, dropwise, a solution of 32.4g isosafrole in 120ml acetone at a rate that kept the reaction mixture from exceeding 40 deg C. This required a bit over 1 hour, and external cooling was used as necessary. Stirring was continued for 16 hours, and care was taken that the slow exothermic reaction did not cause excess heating. An external bath with running water worked well. During this time the solution progressed from an orange color to a deep red. All volatile components were removed under vacuum which yielded some 60g of a very deep residue. This was dissolved in 60ml of MeOH (methyl alcohol -- methanol), treated with 360ml of 15% H2SO4 (sulfuric acid), and heated for 3 hours on the steam bath. After cooling the mixture was extracted with 3x75ml Et2O (diethyl ether) or C6H6 (benzene). Its recommended that, the pooled extracts can washed -- first with H2O and then with dilute NaOH (sodium hydroxide). Then the solvent is removed under vacuum to afford 20.6g 3,4-methylenedioxyphenylacetone (3,4-methylenedioxybenzyl methyl ketone). The final residue may be distilled at 2.0mm/108-112 deg C, or at about 160 deg C at the water pump.
Add 23g 3,4-methylenedioxyphenylacetone to 65g HCONH2 (formamide) and heat at 190 deg for five hours. Cool, add 100ml H20, extract with C6H6 (benzene) and evaporate in vacuum the extract. Add 8ml MeOH (methyl alcohol -- methanol) and 75ml 15% HCl to residue, heat on water bath two hours and extract in vacuum (or basify with KOH and extract the oil with benzene and dry, evaporate in vacuum) to get 11.7 g 3,4-methylenedioxyamphetamine (MDA).
To produce MDMA substitute N-methylformamide for formamide in the above synthesis.
This is a less yealding method usually producing only MDA. It is a two step procedure first reacting safrole with hydrobromic acid to give 3,4-methylenedi- oxyphenyl-2-bromopropane, and then taking this material and reacting it with either ammonia or methylamine to yield MDA or MDMA respectively. This procedure has the advantages of not being at all sensitive to batch size, nor is it likely to "run away" and produce a tarry mess. It shares with the Ritter reaction the advantage of using cheap, simple, and easily available chemicals.
The sole disadvantage of this method is the need to do the final reaction with ammonia or methylamine inside a sealed pipe. This is because the reaction must be done in the temperature range of 120- 140 C, and the only way to reach this temperature is to seal the reactants up inside of a bomb. This is not particularly dangerous, and is quite safe if some simple precautions are taken.
The first stage of the conversion, the reaction with hydrobromic acid, is quite simple, and produces almost a 100% yield of the bromi- nated product. See the Journal of Biological Chemistry, Volume 108 page 619. The author is H.E. Carter. Also see Chemical Abstracts 1961, column 14350. The following reaction takes place:
To do the reaction, 200 ml of glacial acetic acid is poured into a champagne bottle nestled in ice. Once the acetic acid has cooled down, 300 grams (200 ml) of 48% hydrobromic acid is slowly added with swirling. Once this mixture has cooled down, 100 grarns of safrole is slowly added with swirling. Once the safrole is added, the cheap plastic stopper of the champagne bottle is wired back into place, and the mixture is slowly allowed to come to room temperature with occasional shaking. After about 12 hours the original two layers will merge into a clear red solution. In 24 hours, the reaction is done. The chemist carefully removes the stopper from the bottle, wearing eye protection. Some acid mist may escape from around the stopper.
The reaction mixture is now poured onto about 500 grams of crushed ice in a 1000 or 2000 ml beaker. Once the ice has melted, the red layer of product is separated, and the water is extracted with about l00 ml of petroleum ether or regular ethyl ether. The ether extract is added to the product, and the combined product is washed first with water, and then with a solution of sodium carbonate in water. The purpose of these washings is to remove HBr from the product. One can be sure that all the acid is removed from the product when some fresh carbonate solution does not fizz in contact with the product.
Once all the acid in the product is removed, the ether must be removed from it. This is important because if the ether were allowed to remain in it, too much pressure would be generated in the next stage inside of the bomb. Also, it would interfere with the formation of a solution between the product and methylamine or ammonia. It is not necessary to distill the product because with a yield of over 90%, the crude product is pure enough to feed into the next stage. To remove the ether from the product, the crude product is poured into a flask, and a vacuum is applied to it. This causes the ether to boil off. Some gentle heating with hot water is quite helpful to this process. The yield of crude product is in the neighborhood of 200 grams.
With the bromo compound in hand, it is time to move onto the next step which gives MDA or MDMA. The bromo compound reacts with ammonia or methylamine to give MDA or MDMA.
To do the reaction, 50 grams of the bromo compound is poured into a beaker, and 200 ml of concentrated ammonium hydroxide (28% NH3) or 40% methylamine is added. Next, isopropyl alcohol is added with stirring until a nice smooth solution is formed. It is not good to add too much alcohol because a more dilute solution reacts slower. Now the mixture is poured into a pipe "bomb." This pipe should be made of stainless steel, and have fine threads on both ends. Stainless steel is preferred because the HBr given off in the reaction will rust regular steel. Both ends of the pipe are securely tightened down. The bottom may even be welded into place. Then the pipe is placed into cooking oil heated to around 130 C. This temperature is maintained for about 3 hours or so, then it is allowed to cool. Once the pipe is merely warm, it is cooled down some more in ice, and the cap unscrewed.
The reaction mixture is poured into a distilling flask, the glass- ware rigged for simple distillation, and the isopropyl alcohol and excess ammonia or methylamine is distilled off. When this is done, the residue inside the flask is made acid with hydrochloric acid. If indicating pH paper is available, a pH of about 3 should be aimed for. This converts the MDA to the hydrochloride which is water soluble. Good strong shaking of the mixture ensures that this conversion is complete. The first stage of the purification is to recover unreacted bromo compound. To do this, 200 to 300 ml of ether is added. After some shaking, the ether layer is separated. It contains close to 20 grams of bromo compound which may be used again in later batches.
Now the acid solution containing the MDA is made strongly basic with lye solution. The mixture is shaken for a few minutes to ensure that the MDA is converted to the free base. Upon sitting for a few minutes, the MDA floats on top of the water as a dark colored oily layer. This layer is separated and placed into a distilling flask. Next, the water layer is extracted with some toluene to get out the remaining MDA free base. The toluene is combined with the free base layer, and the toluene is distilled off. Then a vacuum is applied, and the mixture is fractionally distilled. A good aspirator with cold water will bring the MDA off at a temperature of 150 to 160 C. The free base should be clear to pale yellow, and give a yield of about 20 ml. This free base is made into the crystalline hydrochloride by dissolving it in ether and bubbling dry HCl gas through it.
Biology Common Forms Other Names
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